Living organisms possess various mechanisms for preventing disease states. For instance, some organisms have immune systems that can recognize proteins on pathogens and tumor cells and subsequently neutralize or kill these cells. By way of example, the mammalian immune system provides both humoral-mediated and cellular-mediated immunological defenses. The humoral arm (e.g., B-cells) manufactures antibodies that can neutralize invading pathogens and tumor cells. The cellular arm employs cytotoxic (e.g., CD8+ T cells) and natural killer cells to kill cells recognized as foreign or otherwise abnormal.
CD8+ T cells kill infected cells if they recognize short (approximately 8-11 amino-acid long) sequences (epitopes) of viral protein in association with Major Histocompatibility Complex class 1 (MHC-1) molecules on a cell's surface. These epitopes are generated by normal digestive processes within the cell and are transported to the cell surface where they are presented to CD8+ T cells in association with MHC-I molecules. The particular epitopes that can be presented by a cell depend on the type of MHC-I molecules expressed by the organism. The human MHC molecule is sometimes referred to as the Human Leukocyte Antigen (HLA). The major human MHC-1 genes are referred to as HLA-A, HLA-B and HLA-C. HLA genes are the most polymorphic of all human genes. Indeed, hundreds of HLA-A, HLA-B, and HLA-C alleles have been identified in the human population.
Pathogenic organisms may sometimes mutate and these mutations may allow the organism to evade a host's defense systems. Moreover, subsequent exposure to the host's natural defenses or available therapies lead to the selection of those pathogens most fit to escape the host's natural defenses as well as those less susceptible to available treatments. Thus, pathogen evolution may be driven by the selective pressures of the host's defenses/therapies. Similarly, the vast polymorphisms exhibited by HLA molecules may be driven by the by co-evolving infectious disease threats. This process of evolution and co-evolution is particularly evident in viruses like the human immunodeficiency virus (HIV), herpes viruses and hepatitis viruses such as hepatitis C virus (HCV).
Various therapies have been directed at augmenting an organism's immune system in order to fight disease. By way of example, vaccinations are widely used to stimulate an immune response to a particular organism (e.g., small pox, polio, etc.) and have even been used to fight tumors (e.g., melanoma). Vaccines may be designed to stimulate humoral immunity, cellular immunity or both humoral and cellular immunity.